Highly purified biologically active alpha-1-antitrypsins (alpha1AT's) are being isolated from plasma using gel exclusion chromatography, affinity chromatography, and DEAE ion exchange chromatography. Isolated preparations of alpha1AT, trace-labeled with radioiodine, are being used to obtain data on the turnover of alpha1AT in normal subjects, patients with alpha1AT deficiency and their relatives and patients with chronic hepatocellular disease. The protease inhibitor phenotypes of subjects donating plasma for isolation of alpha1AT and subjects undergoing alpha1AT turnover studies are determined. Alpha1AT's, isolated from normal subjects (phenotype PiMM) and from patients with alpha1AT deficiency (phenotype PiZZ) have different degrees of sialylation. Each is labeled with a different isotope of iodine and the metabolism of the two labeled preparations are compared in the same individuals. In addition, the metabolism in vivo of alpha1AT which as been desialylated in vitro is being studied. The relationship between the degree of desialylation of alpha1AT and its rate of catabolism and the extent to which decreased hepatic release or increased hepatic uptake of alpha1AT contributes to the low plasma concentrations of alpha1AT deficiency are being determined.